rs376974746
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000233242.5(APOB):āc.8693T>Cā(p.Leu2898Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000874 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L2898L) has been classified as Likely benign.
Frequency
Consequence
ENST00000233242.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.8693T>C | p.Leu2898Pro | missense_variant | 26/29 | ENST00000233242.5 | NP_000375.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.8693T>C | p.Leu2898Pro | missense_variant | 26/29 | 1 | NM_000384.3 | ENSP00000233242 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251376Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135854
GnomAD4 exome AF: 0.0000937 AC: 137AN: 1461812Hom.: 0 Cov.: 37 AF XY: 0.0000880 AC XY: 64AN XY: 727214
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74330
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 16, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 08, 2024 | Identified in a cohort of dyslipidemia patients in published literature (PMID: 32041611); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30076208, 32041611) - |
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 10, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 07, 2021 | - - |
Hypercholesterolemia, familial, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Robarts Research Institute, Western University | Jan 02, 2018 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 29, 2021 | The p.L2898P variant (also known as c.8693T>C), located in coding exon 26 of the APOB gene, results from a T to C substitution at nucleotide position 8693. The leucine at codon 2898 is replaced by proline, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at